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PXD007851

PXD007851 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA Chemproteomics Approach to Query the Degradable Kinome Using a Multi-kinase Degrader
DescriptionHeterobifunctional molecule that recruits E3 ubiquitin ligases, such as cereblon, for targeted protein degradation is an emerging pharmacological strategy. A major unanswered question is how generally applicable this strategy is to all protein targets. In this study, we designed a multi-kinase degrader by conjugating a highly promiscuous kinase inhibitor with a cereblon-binding ligand, and used quantitative proteomics to discover 28 kinases, including BTK, PTK2, PTK2B, FLT3, AURKA, AURKB, TEC, ULK1, ITK and 9 members of the CDK family, as degradable. This set of kinases is only a fraction of the intracellular targets bound by the degrader, demonstrating that successful degradation requires more than target engagement. The results guided us to develop selective degraders for FLT3 and BTK, with potentials to improve disease treatment. Together, this study demonstrates an efficient approach to triage a gene family of interest to identify readily degradable targets for further studies and pre-clinical developments.
HostingRepositoryPRIDE
AnnounceDate2017-11-08
AnnouncementXMLSubmission_2018-05-23_06:17:32.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEric Fischer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-09-27 02:35:42ID requested
12017-11-08 00:04:17announced
22018-05-23 06:17:34announcedUpdated publication reference for PubMed record(s): 29129717.
Publication List
Huang HT, Dobrovolsky D, Paulk J, Yang G, Weisberg EL, Doctor ZM, Buckley DL, Cho JH, Ko E, Jang J, Shi K, Choi HG, Griffin JD, Li Y, Treon SP, Fischer ES, Bradner JE, Tan L, Gray NS, A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader. Cell Chem Biol, 25(1):88-99.e6(2018) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: kinase
Contact List
Eric S. Fischer
contact affiliationBCMP, Harvard Medical School, Boston, USA Cancer Biology, Dana-Farber Cancer Institute, Boston, USA
contact emaileric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliationDana-Farber Cancer Institute
contact emaileric_fischer@dfci.harvard.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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